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German Ambassador visits Max Planck Bristol Centre

Profs Dek Woolfson, Jens Marklof, Christiane Schaffitzel, His Excellency Miguel Berger, Profs Imre Berger, Nigel Savery, Stephen Mann and Daniela Schmidt pose in front of Luke Jerram's Extinction Bell artwork at University of Bristol.
From left to right: Profs Dek Woolfson, Jens Marklof, Christiane Berger-Schaffitzel, His Excellency Miguel Berger, Profs Imre Berger, Nigel Savery, Stephen Mann and Daniela Schmidt (Photo: Bhagesh Sachania Photography)

The German Ambassador to the UK, His Excellency Miguel Berger, visited the University of Bristol on 11 November, to meet Professor Evelyn Welch, the University’s Vice-Chancellor and President, and to discuss opportunities for UK-Germany education and research collaboration.

The Ambassador, accompanied by Dr Felix Karstens from the Embassy’s Political Department, met researchers from the Max Planck Bristol Centre for Minimal Biology, as well as the University’s Senior team, and staff and students in the School of Modern Languages.

Prof Dek Woolfson, Prof Imre Berger, His Excellency Miguel Berger, and Prof Stephen Mann pose outside the MAx Planck Bristol Centre lab.
The Ambassador meets three of the Directors of the Max Planck Bristol Centre. From left: Prof Dek Woolfson, Prof Imre Berger, His Excellency Miguel Berger, & Prof Stephen Mann (Photo: Bhagesh Sachania Photography)

During their tour, they were also shown the GW4 Facility for High-Resolution Electron Cryo-Microscopy in the University’s Life Sciences Building, which underpins ground-breaking research by providing analysis tools to researchers enabling them to study the molecular processes responsible for cell function or malfunction.

Prof Nigel Savery, Dr Felix Karstens, His Excellency Miguel Berger and Prof Christiane Berger Schaffitzel in the GW4 Facility for High-Resolution Electron Cryo-Microscopy at University of Bristol.
From left: Prof Nigel Savery, Dr Felix Karstens, His Excellency Miguel Berger and Prof Christiane Berger-Schaffitzel in the GW4 Facility for High-Resolution Electron Cryo-Microscopy (Photo: Bhagesh Sachania Photography)

Dr Mark Allinson, the University’s Associate Pro Vice-Chancellor (Learning and Teaching), said: “We are honoured to have hosted a visit from the German Ambassador. Bristol is fortunate to have a number of firmly embedded partnerships with Germany through its research and language teaching, and we hope today’s visit will further strengthen those links with our European peers.”

(A version of this story was originally published by University of Bristol)

Pioneering research using bacteria brings scientists a step closer to creating artificial cells with lifelike functionality

Amoeba-shaped bacteriogenic protocell: membrane (red boundary); nucleus (blue); cytoskeleton (red filaments); vacuole (red circle); ATP production (green). Scale bar, 5 μm. Image credit: Professor Stephen Mann and Dr Can Xu

Scientists have harnessed the potential of bacteria to help build advanced synthetic cells which mimic real life functionality. The research, led by the University of Bristol and published in Nature, makes important progress in deploying synthetic cells, known as protocells, to more accurately represent the complex compositions, structure, and function of living cells.

Establishing true-to-life functionality in protocells is a global grand challenge spanning multiple fields, ranging from bottom-up synthetic biology and bioengineering to origin of life research.  Previous attempts to model protocells using microcapsules have fallen short, so the team of researchers turned to bacteria to build complex synthetic cells using a living material assembly process.

Professor Stephen Mann from the University of Bristol’s School of Chemistry, and the Max Planck Bristol Centre for Minimal Biology, together with colleagues Drs Can Xu, Nicolas Martin (currently at the University of Bordeaux) and Mei Li in the Bristol Centre for Protolife Research have demonstrated an approach to the construction of highly complex protocells using viscous micro-droplets filled with living bacteria as a microscopic building site.

In the first step, the team exposed the empty droplets to two types of bacteria. One population spontaneously was captured within the droplets while the other was trapped at the droplet surface.

Then, both types of bacteria were destroyed so that the released cellular components remained trapped inside or on the surface of the droplets to produce membrane-coated bacteriogenic protocells containing thousands of biological molecules, parts and machinery.

The researchers discovered that the protocells were able to produce energy-rich molecules (ATP) via glycolysis and synthesize RNA and proteins by in vitro gene expression, indicating that the inherited bacterial components remained active in the synthetic cells.

Further testing the capacity of this technique, the team employed a series of chemical steps to remodel the bacteriogenic protocells structurally and morphologically. The released bacterial DNA was condensed into a single nucleus-like structure, and the droplet interior infiltrated with a cytoskeletal-like network of protein filaments and membrane-bounded water vacuoles.

As a step towards the construction of a synthetic/living cell entity, the researchers implanted living bacteria into the protocells to generate self-sustainable ATP production and long-term energization for glycolysis, gene expression and cytoskeletal assembly. Curiously, the protoliving constructs adopted an amoeba-like external morphology due to on-site bacterial metabolism and growth to produce a cellular bionic system with integrated life-like properties.

Corresponding author Professor Stephen Mann said: “Achieving high organisational and functional complexity in synthetic cells is difficult especially under close-to-equilibrium conditions. Hopefully, our current bacteriogenic approach will help to increase the complexity of current protocell models, facilitate the integration of myriad biological components and enable the development of energised cytomimetic systems.”

First author Dr Can Xu, Research Associate at the University of Bristol, added: “Our living-material assembly approach provides an opportunity for the bottom-up construction of symbiotic living/synthetic cell constructs. For example, using engineered bacteria it should be possible to fabricate complex modules for development in diagnostic and therapeutic areas of synthetic biology as well as in biomanufacturing and biotechnology in general.” 

(This story was originally published by University of Bristol)

Welcome to EPSRC Doctoral Prize Fellow Rafa Moreno Tortolero

Rafael Orlando Moreno TortoleroWe are excited to introduce the newest member of the Max Planck Bristol Centre for Minimal Biology.

Rafael Moreno Tortolero has been awarded an EPSRC Doctoral Prize Fellowship to investigate the role of protein aggregates in health and disease.

We asked Rafa to introduce himself.

“I am a Venezuelan materials engineer by training (Simón Bolívar University, Venezuela), with an MSc in functional nanomaterials, a PhD in chemistry (University of Bristol, UK) and a penchant for fundamental medical research.

The latter has informed every step of my career so far. I worked with silk protein during my PhD to fabricate tissue engineering scaffolds. There, I stumbled with fundamental aspects of the protein that led me to continue my journey as an EPSRC Doctoral Prize Fellow at the very prestigious Max Planck Bristol Centre, under the mentorship of the eminent Prof. Imre Berger.

In this fellowship, I will explore a fascinating subject: the relationship between functional and aberrant protein aggregates with health and disease. More specifically, the relationship between silk and amyotrophic lateral sclerosis (ALS). Both biological phenomena, one producing healthy ex-vivo protecting structures (silk) and the other causing a devastating neuronal disease, are perhaps more related than previously thought and are at the centre of my research. Inspired by the silk production machinery, removal mechanisms of toxic ALS-related aggregates will be explored through standard biochemical and biophysical techniques. Aiming to discover protein-based palliative treatments for this devastating and untreatable disease.”

Prof Imre Berger elected Fellow of Academy of Medical Sciences

Imre BergerImre Berger, Professor of Biochemistry and Chemistry and Director of the Max Planck Bristol Centre for Minimal Biology, has been elected as a Fellow of the Academy of Medical Sciences for his outstanding contributions to biomedical science and notable discoveries during the COVID-19 pandemic.

This year, the Academy has elected 60 outstanding biomedical and health scientists to its Fellowship for their remarkable contributions to biomedical and health science and their ability to generate new knowledge and improve the health of people everywhere.

Professor Berger’s work includes a number of significant breakthroughs in the fight against COVID-19. His team discovered a druggable pocket in the SARS-CoV-2 Spike protein that could be used to stop the virus from infecting human cells, blocking transmission and forestalling severe COVID-19 disease. At the height of the pandemic, his team showed that exposing the SARS-CoV-2 coronavirus to a free fatty acid called linoleic acid locks the Spike protein into a closed, non-infective form inhibiting the virus’ ability to enter and multiply in cells, stopping it in its tracks.

The findings, published in Science, are now being used to develop new cost-effective treatments against all pathogenic coronavirus strains by Bristol-based Halo Therapeutics Ltd. The biotech company, co-founded by Professor Berger, is currently preparing for in-human clinical trials.

Other notable breakthroughs include the discovery that SARS-CoV-2-infected individuals could have several different SARS-CoV-2 variants hidden away from the immune system in different parts of the body, which may make complete clearance of the virus from infected persons, by their own antibodies, or by therapeutic antibody treatments, much more difficult.

Professor Berger is also pioneering new vaccine technologies. His team developed the ADDomer™, a thermostable vaccine platform for highly adaptable, easy-to-manufacture, rapid-response vaccines to combat present and future infectious diseases including COVID-19.  A key benefit of the platform is the speed with which candidate vaccines can be identified and could be manufactured in large quantities without refrigeration, significantly facilitating distribution world-wide. Vaccine innovator start-up Imophoron Ltd, co-founded by Professor Berger, is bringing ADDomer™-based vaccines to the market.

Professor Imre Berger said: “I am honoured to have been elected to the Fellowship of the Academy of Medical Sciences.

“I am also deeply grateful for the great effort by the fantastic scientists, technicians, engineers and students in my team, past and present, and the collaborators whom I have the privilege to work with. As researchers, the pandemic has presented us with immense challenges which has only highlighted the importance of scientific endeavour and medical science. It is therefore rewarding to have had our contributions recognised by the Academy that also seeks to improve and support advances in this field.”

Professor Dame Anne Johnson FMedSci, President of the Academy of Medical Sciences said: “Each of the new Fellows has made important contributions to the health of our society. The diversity of biomedical and health expertise within our Fellowship is a formidable asset that in the past year has informed our work on critical issues such as tackling the COVID-19 pandemic, understanding the health impacts of climate change, addressing health inequalities, and making the case for funding science. The new Fellows of 2022 will be critical to helping us deliver our ambitious 10-year strategy that we will launch later this year.”

The new Fellows will be formally admitted to the Academy on Monday 27 June 2022.

(This news story was originally published by the University of Bristol)

Research Associate in Synthetic Virus-derived Nanosystems (SVNs) for next generation protein and DNA delivery

** Applications are now closed **

As part of the Max Planck Bristol Centre for Minimal Biology (MPBC), a post-doctoral position is available to develop synthetic virus-derived nanosystems as next-generation protein and DNA delivery tools for genome engineering. This post is available for two years in the first instance, with potential to extend to July 2025.

The position is associated with the synthetic and structural biology laboratories of Prof Imre Berger (Biochemistry and Chemistry). The post holder would work in the newly refurbished laboratory for the MPBC, which is housed in the University of Bristol’s School of Chemistry and is a shared space with other MPBC researchers associated with the laboratories of Prof Dek Woolfson (Chemistry and Biochemistry) and Steve Mann FRS (Chemistry; protocell research). As with all projects in the MPBC, it is anticipated that the work will develop in collaboration with our Max Planck partners in Germany.

The position would be best suited to a talented, creative and ambitious early career researcher with a keen interest in synthetic and minimal biology of protein and DNA delivery systems. Essential skills for this role would include: experience with molecular biology and tissue culture techniques, construction and delivery of multifunctional synthetic gene circuitry in mammalian cells, CRISPR and non-CRISPR gene editing technologies and functional analysis by light and electron microscopy and/or FACS.

Additional info

  • More information, including the job description and how to apply, is available here.
  • For informal enquiries, please contact Professor Imre Berger (imre.berger@bristol.ac.uk)
  • The closing date for applications is 12 April 2022. 

Research Associate in protein design in the cell

** Applications are now closed **

As part of the recently established Max Planck-Bristol Centre for Minimal Biology (MPBC), a post-doctoral Research Associate position is available to develop de novo protein design in bacterial and eukaryotic cells. Funding for this post is available until July 2025.

The position is associated with the protein design laboratory of Prof Dek Woolfson (Chemistry and Biochemistry). The post holder would work in the newly refurbished laboratory for the MPBC, which is housed in the University of Bristol’s School of Chemistry and is a shared space with other MPBC researchers associated with the laboratories of Profs Imre Berger (Biochemistry; genome engineering) and Steve Mann FRS (Chemistry; protocell research). As with all projects in the MPBC, it is anticipated that the work will develop in collaboration with our Max Planck partners in Germany.

The position would be best suited to a talented and ambitious early career researcher with an interest in applying de novo protein design in synthetic and minimal biology. Essential skills for this role would include: experience in molecular cell biology in bacteria and/or eukaryotes, including the design and expression of synthetic genes in E. coli and/or HeLa cells or similar; plus biochemical and biophysical characterisation of proteins in cells using light and electron microscopy and/or FACS. Experience in the de novo design, synthesis, and structural characterisation of synthetic peptides and proteins would be desirable, but it is not essential for this post.

Additional info

  • More information, including the job description and how to apply, is available here.
  • For informal enquiries, please contact Dek Woolfson via email: d.n.woolfson@bristol.ac.uk
  • The closing date for applications is 20 March 2022. 

Bristol’s pioneering COVID-19 research prompts French Embassy visit

Representatives from the French Embassy visited University labs on 10 December to see some of the innovative COVID-19 research being undertaken at Bristol, including work on ADDomer™, a thermostable vaccine platform being developed by Bristol scientists to combat emerging infectious diseases.

Dr Rachel Millet and Arthur Belaud from the Embassy’s Innovation Branch, which seeks to drive France-UK business enterprise, met with scientists Professor Imre Berger and Frederic Garzoni, founders of Imophoron Ltd, the biotech start-up developing ADDomer that uses technology developed at an institution in France, and recently secured £4 million investment.

L to R: Arthur Belaud from the French Embassy, Dr Anne Westcott from the University, Dr Rachel Millet from the French Embassy and Professor Imre Berger at the University’s Max Planck Bristol Centre for Minimal Biology

During the visit, the delegation took a tour of labs in the University’s Max Planck-Bristol Centre for Minimal Biology (MPBC), the GW4/Wellcome Trust Cryo-EM facility led by Prof Christiane Schaffitzel, and Science Creates, the Bristol-based incubator, which is operated in partnership with the University and supports scientists and engineers in commercialising ground-breaking innovations. Having recently opened its second facility in the city’s Old Market, the party met with Science Creates founder and Bristol graduate Dr Harry Destecroix to discuss the future of deep-tech eco-systems.

Professor Imre Berger, Director of Bristol’s Max Planck Centre for Minimal Biology, said: “We are honoured to host this visit from the French Embassy’s Innovation Branch to share knowledge and showcase the pioneering research that is being done in collaboration with our European colleagues and institutions.”

Press release issued: 10 December 2021 on University of Bristol News and Features~ article here.

Protocells Spring Into Action

A Max Planck-led team of international scientists with an interest in protoliving technologies, has recently published research which paves the way to building new semi-autonomous devices with potential applications in miniaturized soft robotics, microscale sensing and bioengineering.

In a series of experiments, the researchers successfully embedded tens of thousands of artificial cell-like entities (protocells) within helical filaments of a polysaccharide hydrogel to produce tiny free-standing springs that are chemically powered from within.

Protocell-based micro-actuator; single giant protocells (red) are seen attached at both ends of a mechanically energized hydrogel filament (green).

Professor Stephen Mann, co-Director of the Max Planck Bristol Centre for Minimal Biology (MPBC) at Bristol, said: “We have a longstanding interest in protoliving technologies. One key challenge is how to interface protocell communities with their environment to produce functional relationships. The new work provides a step in this direction as it illustrates how endogenous chemical processes can be coupled to their energized surroundings to produce a programmable chemo-mechanical micro-system”.

Dr Ning Gao, also at the MPBC and School of Chemistry at the University of Bristol added: “We hope that our approach will motivate the fabrication of new types of soft adaptive microstructures that operate via increased levels of autonomy.” [Read the full article on the University of Bristol news page]

Paper:

Chemical-mediated translocation in protocell-based microactuators,’ by  Gao N, Li M, Tian L, Patil A J, Kumar P B V V Sand Mann S in Nature Chemistry.

German Ambassador visits the University of Bristol

On Wednesday 2 September, the German Ambassador to the Court of St James’s, Andreas Michaelis, paid a visit to the University of Bristol. Michaelis came to discuss with University representatives the opportunities to collaborate with Germany across research, education and mobility. The visit was a significant step in building and fostering the University’s relationship with the new Ambassador, in his first official trip to the UK outside of London.

The delegation toured the Max Planck Centre for Minimal Biology in the School of Chemistry and the GW4 Facility for High-Resolution Electron Cryo-Microscopy in the Life Sciences Building. Established in 2019, the Max Planck Bristol Centre consists of Directors based in both Bristol and Germany in a truly interdisciplinary and international partnership, set up by the University of Bristol and the Max Planck Society. The Centre pursues game-changing research and postgraduate training in the emerging field of minimal biology to address some of the most complex challenges in fundamental science.

Eatablishment of the Max Planck Bristol Centre in 2019. Professor Hugh Brady, Vice-Chancellor and President of the University of Bristol, and Professor Martin Stratmann, President of the Max Planck Society.

The GW4 Facility for High-Resolution Electron Cryo-Microscopy is closely aligned with the Wolfson Bioimaging Facility and provides world class cryo-microscopy and analysis tools, enabling researchers from diverse disciplines across the Great West region and beyond to study molecular processes using single-particle cryo-EM or cryo-tomography.

Director of the Max Planck Bristol Centre, Imre Berger, discussed the importance of international cooperation in science with Herr Michaelis on his tour of campus. The German delegation also met with Bristol Heads of School and Pro Vice-Chancellors, as well as members of the Bristol Max Planck and Cryo-EM facilities to observe our joint Europe-Bristol research endeavours. The Pro Vice-Chancellor for Global Engagement Erik Lithander

said: “We were delighted to be able to welcome the Ambassador to the University to have the opportunity to showcase some of the terrific research being done in collaboration with German colleagues and institutions. The University of Bristol is determined to keep European collaboration at the centre of its research strategy, and opportunities such as the Ambassador’s visit are an excellent way to accentuate this.”

German Ambassador Visit, 2 September 2020. Andreas Michaelis, German Ambassador to the Court of St James’s and Professor Imre Berger, Director of the Max Planck Bristol Centre for Minimal Biology discussing the importance of international cooperation in science.

**PhD Bioscience Opportunity- Taking De Novo Protein Design And Assembly Into Bacterial Cells**

Taking De Novo Protein Design And Assembly Into Bacterial Cells

Click here to apply.

Application deadline: Monday 2nd December 2019 (Midnight)
Host Institution: University of Bristol
Commencing: September 2020
Main Supervisor: Prof Dek Woolfson
Second Supervisor(s): Prof Nigel Savery and Prof Paul Verkade

Advancing the frontiers of bioscience discovery, the South West Biosciences Doctoral Training Partnership (SWBio DTP) aims to provide PhD students with outstanding interdisciplinary research training.


Project Description:

De novo protein design is the process of building entirely new protein sequences to adopt stable structures from scratch, and programming these further to perform desired functions. It is distinct from protein engineering, which aims to improve the stabilities and functions of natural proteins for given applications. In basic science, de novo protein design is the acid test of our understanding of sequence-to-structure/function relationships of natural proteins. In frontier bioscience, it presents possibilities for generating protein structures not yet observed in nature, i.e. the so-called ‘dark matter of protein-structure space’ (Woolfson et al., (2015) Curr Opin Struct Biol 33 16). In applied science and biotechnology, it offers routes to hyperstable proteins with functions not performed by natural proteins.

Over the past 5 – 10 years, protein designers’ abilities to deliver stable de novo proteins that fold and assemble as prescribed has advanced considerably. This has come through improvements in our understanding of sequence-to-structure relationships in proteins, advances in computational design methods, the reduced cost of synthetic peptides and genes, and increased speeds of high-throughput screening of protein libraries. These advances set new targets for the field of de novo protein design. One of these challenges is to take de novo proteins directly into cells to enhance and augment natural biological systems.

Our research groups—Woolfson, Savery and Verkade—have worked together for 5 years to help establish this nascent field of ‘protein design in the cell’. Our achievements include the design,
assembly, visualisation and functionalisation of a de novo cytoskeleton in E. coli (Lee et al. (2018) Nat Chem Biol 14 142); and the delivery of a series of de novo protein-protein interactions that operate in E. coli and substitute for protein-protein-interactions domains that control transcription (Smith et al.(2019) ACS Synth Biol 8 1284).

The proposed PhD project builds on these international and local developments in de novo protein design, and the collaborative environment that we have established, to advance protein design in the cell. Specifically, we will take protein-design modules that the Woolfson group has built and characterised to high resolution, combine them to make functional de novo assemblies in E. coli using synthetic-biology methods established by the Savery group, and visualise the assemblies directly in cells using the Verkade group’s expertise in light and electron microscopy. Our overall aim is to design de novo proteins that fold, assemble, disassemble and function on command in living cells.


How to apply:

To submit an application, please click here.
For eligibility requirements, please click here.
For further information, please contact the listed supervisor: Prof Dek Woolfson